On the direct scavenging activity of melatonin towards hydroxyl and a series of peroxyl radicals

The reactions of melatonin (MLT) with hydroxyl and several peroxyl radicals have been studied using the Density Functional Theory, specifically the M05-2X functional. Five mechanisms of reaction have been considered: radical adduct formation (RAF), Hydrogen atom transfer (HAT), single electron transfer (SET), sequential electron proton transfer (SEPT) and proton coupled electron transfer (PCET). It has been found that MLT reacts with OH radicals in a diffusion-limited way, regardless of the polarity of the environment, which indicates that MLT is an excellent OH radical scavenger. The calculated values of the overall rate coefficient of MLT + (OH)-O-center dot reaction in benzene and water solutions are 2.23 x 10(10) and 1.85 x 10(10) M-1 s(-1), respectively. MLT is also predicted to be a very good (OOCCl3)-O-center dot scavenger but rather ineffective for scavenging less reactive peroxyl radicals, such as alkenyl peroxyl radicals and (OOH)-O-center dot. Therefore it is concluded that the protective effect of MLT against lipid peroxidation does not take place by directly trapping peroxyl radicals, but rather by scavenging more reactive species, such as (OH)-O-center dot, which can initiate the degradation process. Branching ratios for the different channels of reaction are reported for the first time. In aqueous solutions SEPT was found to be the main mechanism for the MLT + (OH)-O-center dot reaction, accounting for about 44.1% of the overall reactivity of MLT towards this radical. The good agreement between the calculated and the available experimental data, on the studied processes, supports the reliability of the results presented in this work.